4β-S-(benzoxazole-2-)-4-deoxy-4'-demethylepipodophyllotoxin

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 4β-S-(benzoxazole-2-)-4-deoxy-4'-demethylepipodophyllotoxin
• 英文别名: (5S,5aR,8aR,9R)-5-(1,3-benzoxazol-2-ylsulfanyl)-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
• 化学式: C₂₈H₂₃NO₈S
• 分子量: 533.559
• InChiKey: XLSHUYGGAJOZJU-GHALKUQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  135
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4'-去甲基表鬼臼毒素 、 2-巯基苯并恶唑 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以60%的产率得到4β-S-(benzoxazole-2-)-4-deoxy-4'-demethylepipodophyllotoxin
  参考文献：
  名称：

  Discover the leading compound of 4β-S-(5-fluorobenzoxazole)-4-deoxy-4′-demethylepipodophyllotoxin with millimolar-potency toxicity by modifying the molecule structure of 4′-demethylepipodophyllotoxin

  摘要：

  4 '-Demethylepipodophyllotoxin (DMEP) derivatives are broad-spectrum and potent antitumor leading compound. Because of their unacceptable toxicity, DMEP derivatives often failed in the development of new drug. Until now, there was no report on the millimolar-potency toxicity of DMEP derivatives by modifying the molecule structure of DMEP. For the first time, this work discovered leading compounds with millimolar-potency toxicity by modifying the molecule structure of DMEP. The IC50 value of 4 beta-S-(5-fluorobenzoxazole-2-)-4-deoxy-4 '-demethylepipodophyllotoxin (Compound 2) was around 323.4 2000.9 mu M on human healthy cells (i.e., HL-7702, H8, MRC-5 and HMEC), which was significantly reduced by 171-1999 times than podophyllotoxin (1.0-2.6 mu M) and 9-80 times than etoposide (21.5 75.4 mu M). Compared with the treatment of etoposide, DNA repair proteins HMGB1 and PARK7 were specifically activated and the expression of anti-apoptotic proteins were up-regulated in HL-7702 cells after the treatment of Compound 2. These indicated the toxicity of Compound 2 was synergistically reduced by DNA repair and anti-apoptosis pathway. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.09.022